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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular evolution 28 (1988), S. 131-135 
    ISSN: 1432-1432
    Keywords: Rate of amino acid substitutions ; Amino acid composition ; Serine proteinase inhibitors ; Ovomucoids ; Spi-2 ; Neutral theory ; Positive Darwinian selection ; Serpins ; Kunitz-type inhibitors ; Kazal-type inhibitors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary In at least two instances involving serine proteinase inhibitors it has been shown that functionally important sites evolve faster and exhibit more interspecific variability than functionally neutral sites. Because these phenomena are difficult to reconcile with the neutral theory of molecular evolution, it has been suggested that the accelerated rate of amino acid substitution at the reactive sites is brought about by positive Darwinian selection. We show that differences in the amino acid composition in the different regions of proteinase inhibitors can account for the differences in the rates of amino acid substitution. By using an index of protein mutability [D. Graur (1985) J Mol Evol 22∶53–62], we show that the amino acid composition of the reactive center in the ovomucoids andSpi-2 gene products is such that, regardless of function, they are expected to evolve more rapidly than any other polypeptide for which the rate of substitution is known. In addition, the reactive region in theSpi-2 proteins is shown to be free of compositional constraint. Positive Darwinian selection need not be invoked at the present time in these cases.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular evolution 28 (1989), S. 279-285 
    ISSN: 1432-1432
    Keywords: Processed pseudogenes ; Rate of substitution ; Deletions ; Insertions ; Genome size
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The relative rates of point nucleotide substitution and accumulation of gap events (deletions and insertions) were calculated for 22 human and 30 rodent processed pseudogenes. Deletion events not only outnumbered insertions (the ratio being 7∶1 and 3∶1 for human and rodent pseudogenes, respectively), but also the total length of deletions was greater than that of insertions. Compared with their functional homologs, human processed pseudogenes were found to be shorter by about 1.2%, and rodent pseudogenes by about 2.3%. DNA loss from processed pseudogenes through deletion is estimated to be at least seven times faster in rodents than in humans. In comparison with the rate of point substitutions, the abridgment of pseudogenes during evolutionary times is a slow process that probably does not retard the rate of growth of the genome due to the proliferation of processed pseudogenes.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular evolution 36 (1993), S. 327-334 
    ISSN: 1432-1432
    Keywords: Cytochrome b ; Mitochondrial DNA ; Mammalian phylogeny ; Functional constraints ; Coevolution ; Cavia porcellus ; Monodelphis domestica ; Hystrix africaeaustralis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary We have sequenced the mitochondrial cytochrome b gene from the guinea pig, the African porcupine, and a South American opossum. A phylogenetic analysis, which includes 22 eutherian and four other vertebrate cytochrome b sequences, indicates that the guinea pig and the porcupine constitute a natural clade (Hystricomorpha) that is not a sister group to the clade of mice and rats (Myomorpha). Therefore, the hypothesis that the Rodentia is paraphyletic receives additional support. The artiodactyls, the perissodactyls, and the cetaceans form a group that is separated from the primates and the rodents. The 26 sequences are used to study the structure/function relationships in cytochrome b, whose function is electron transport. Most of the amino acid residues involved in the two reaction centers are well conserved in evolution. The four histidines that are believed to ligate the two hemes are invariant among the 26 sequences, but their nearby residues are not well conserved in evolution. The eight transmembrane domains represent some of the most divergent regions in the cytochrome b sequence. The rate of nonsynonymous substitution is considerably faster in the human and elephant lineages than in other eutherian lineages; the faster rate might be due to coevolution between cytochrome b and cytochrome c.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular evolution 28 (1989), S. 286-298 
    ISSN: 1432-1432
    Keywords: Rate of synonymous substitution ; Codon usage ; Nucleotide composition ; Codonanticodon interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Based on the rates of synonymous substitution in 42 protein-codin gene pairs from rat and human, a correlation is shown to exist between the frequency of the nucleotides in all positions of the codon and the synonymous substitution rate. The correlation coefficients were positive for A and T and negative for C and G. This means that AT-rich genes accumulate more synonymous substitutions than GC-rich genes. Biased patterns of mutation could not account for this phenomenon. Thus, the variation in synonymous substitution rates and the resulting unequal codon usage must be the consequence of selection against A and T in synonymous positions. Most of the varition in rates of synonymous substitution can be explained by the nucleotide composition in synonymous positions. Codon-anticodon interactions, dinucleotide frequencies, and contextual factors influence neither the rates of synonymous substitution nor codon usage. Interestingly, the nucleotide in the second position of codons (always a nonsynonymous position) was found to affect the rate of synonymous substitution. This finding links the rate of nonsynonymous substitution with the synonymous rate. Consequently, highly conservative proteins are expected to be encoded by genes that evolve slowly in terms of synonymous substitutions, and are consequently highly biased in their codon usage.
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  • 5
    ISSN: 1432-1432
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular evolution 21 (1985), S. 221-231 
    ISSN: 1432-1432
    Keywords: Retroviruses ; Nucleotide substitution ; Purifying selection ; Reverse transcription ; Grantham's chemical distances
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The patterns of point mutation and nucleotide substitution are inferred from nucleotide differences in three coding and two noncoding regions of retroviral genomes. Evidence is presented in favor of the view that the majority of mutations accumulate at the reverse transcription stage. Purifying selection is apparently very weak at the amino acid level, and almost nonexistent between synonymous codons. The pattern of purifying selection obeys the rules previously established in vertebrates [Gojobori T, Li W-H, Graur D (1982) J Mol Evol 18:360–369]; i.e., the magnitude of purifying selection at the amino acid level is negatively correlated with Grantham's [Grantham R (1974) Science 185: 862–864] chemical distances between the amino acids interchanged. We refute Modiano et al.'s [Modiano G, Battistuzzi G, Motulsky AG (1981) Proc Natl Acad Sci USA 78:1110–1114] hypothesis, according to which the pattern of mutation is preadapted to buffer against deleterious mutations. On the contrary, the pattern of mutation reduces the level of conservativeness from that imposed on the amino acid substitution pattern by the structure of the genetic code. The extraordinarily high rate of nucleotide substitution in retroviruses in comparison with that in other organisms is apparently caused by an extremely high rate of mutation coupled with a lack of stringent purifying selection at both the codon and the amino acid levels.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular evolution 18 (1982), S. 360-369 
    ISSN: 1432-1432
    Keywords: Neutral mutation ; Transitions and transversions ; Functional constraints ; Base content ; Substitution mutagenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The pattern of point mutations is inferred from nucleotide substitutions in pseudogenes. The pattern obtained suggests that transition mutations occur somewhat more frequently than transversion mutations and that mutations result more often in A or T than in G or C. Our results are discussed with respect to the predictions from Topal and Fresco's model for the molecular basis of point (substitution) mutations (Nature 263:285–289, 1976). The pattern of nucleotide substitution at the first and second positions of codons in functional genes is quite similar to that in pseudogenes, but the relative frequency of the transition C→T in the sense strand is drastically reduced and those of the transversions C→G and G→C are doubled. The differences between the two patterns can be explained by the observation that in the protein evolution amino acid substitutions occur mainly between amino acids with similar biochemical properties (Grantham, Science 185:862–864, 1974). Our results for the patterns of nucleotide substitutions in pseudogenes and in functional genes lead to the prediction that both the coding and non-coding regions of protein coding genes should have high frequencies of A and T. Available data show that the non-coding regions are indeed high in A and T but the coding regions are low in T, though high in A.
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  • 8
    ISSN: 1432-1432
    Keywords: Directional mutation pressure ; A + T pressure ; G + C pressure ; Synonymous codon sites ; Nonsynonymous codon sites ; Mitochondrial cytochrome b gene ; Metazoa ; Magnoliophyta ; Chlorophyta ; Eumycota
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract We present a new approach for analyzing directional mutation pressure and nucleotide content in protein-coding genes. Directional mutation pressure, the heterogeneity in the likelihood of different nucleotide substitutions, is used to explain the increasing or decreasing guanine-cytosine content (GC%) in DNA and is represented by µD, in agreement with Sueoka (1962, Proc Natl Acad Sci USA 48:582–592). The new method uses simulation to facilitate identification of significant A + T or G + C pressure as well as the comparison of directional mutation pressure among genes, even when they are translated by different genetic codes. We use the method to analyze the evolution of directional mutation pressure and nucleotide content of mitochondrial cytochrome b genes. Results from a survey of 110 taxa indicate that the cytochrome b genes of most taxa are subjected to significant directional mutation pressure and that the gene is subject to A + T pressure in most cases. Only in the anseriform bird Cairina moschata is the cytochrome b gene subject to significant G + C pressure. The GC% at nonsynonymous codon sites decreases proportionately with increasing A + T pressure, and with a slope less than one, indicating a presence of selective constraints. The cytochrome b genes of insects, nematodes, and eumycotes are subject to extreme A + T pressures (µD = 0.123, 0.224, and 0.130) and, in parallel, the GC% of the nonsynonymous codon sites has decreased from about 0.44 in organisms that are not subjected to A + T or G + C pressure to about 0.332, 0.323, and 0.367, respectively. The distribution of taxa according to the GC% at nonsynonymous codon sites and directional mutation pressure supports the notion that variation in these parameters is a phylogenetic component.
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  • 9
    ISSN: 1432-1432
    Keywords: Key words: Symmetrical directional mutation pressure — A+T pressure — G+C pressure — Synonymous codon sites — Nonsynonymous codon sites — Bias correction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract. The most generally applicable procedure for obtaining estimates of the symmetrical, or strand-nonspecific, directional mutation pressure (μD) on protein-coding DNA sequences is to determine the G+C content at synonymous codon sites (P syn), and to divide P syn by twice the arithmetic mean of the G+C content at synonymous codon sites of a large number of randomly generated, synonymously coding DNA sequences (P syn). Unfortunately, the original procedure yields biased estimates of P syn and μD and is computationally expensive. We here present a fast procedure for estimating unbiased μD values. The procedure employs direct calculation of P syn (≈P syn) and two normalization procedures, one for P syn≤P syn and another for P syn≥P syn. The normalization removes a bias sometimes caused by codons specifying arginine, asparagine, isoleucine, and leucine. Consequently, comparison of protein-coding genes that are translated using different genetic codes is facilitated.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular evolution 22 (1985), S. 53-62 
    ISSN: 1432-1432
    Keywords: Rate of amino acid substitution ; Amino acid composition ; Glycine ; Functional constraints
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Based on the rates of amino acid substitution for 60 mammalian genes of 50 codons or more, it is shown that the rate of amino acid substitution of a protein is correlated with its amino acid composition. In particular, the content of glycine residues is negatively correlated with the rate of amino acid substitution, and this content alone explains about 38% of the total variation in amino acid substitution rates among different protein families. The propensity of a polypeptide to evolve fast or slowly may be predicted from an index or indices of protein mutability directly derivable from the amino acid composition. The propensity of an amino acid to remain conserved during evolutionary times depends not so much on its being features prominently in active sites, but on its stability index, defined as the mean chemical distance [R. Grantham (1974) Science 185∶862–864] between the amino acid and its mutational derivatives produced by single-nucleotide substitutions. Functional constraints related to active and binding sites of proteins play only a minor role in determining the overall rate of amino acid substitution. The importance of amino acid composition in determining rates of substitution is illustrated with examples involving cytochrome c, cytochrome b5,ras-related genes, the calmodulin protein family, and fibrinopeptides.
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